Cryptands and other macrocyclic compounds such as crown ethers, spherands, cryptahemispherands, cavitands, calixarenes, resorcinorenes, cyclodextrines, porphyrines and others are well known. (Comprehensive Supramolecular Chemistry Vol. 1-10, Jean-Marie Lehn—Chairman of the Editorial Board, 1996 Elsevier Science Ltd.) Many of them are capable of forming stable complexes with ionic organic and inorganic molecules. Those properties make macrocyclic compounds candidates for various fields, for instance, catalysis, separations, sensors development and others. Cryptands (bicyclic macrocycles) have extremely high affinity to metal ions. The cryptand metal ion complexes are more stable than those formed by monocyclic ligands such as crown ethers (Izatt, R. M., et al., Chemical Reviews 91:1721-2085 (1991)). This high affinity of the cryptands to alkaline and alkaline earth metal ions in water makes them superior complexing agents for the processes where strong, fast and reversible metal ion binding is required. Examples of these processes include separation, preconcentration and detection of metal ions, analysis of radioactive isotopes, ion-exchange chromatography, phase-transfer catalysis, activation of anionic species and others.
Adding moieties with functionality to macrocyclic compounds permits binding of the derivatized macrocycles onto support substrates to provide surface functionalization. Physical adsorption and covalent attachment are two common methods of binding. Cryptand adsorbed polymers have been reported as stationary phases for ion exchange chromatography (Lamb, J. D., et al., J. Chromatogr., 482:367-380 (1989); Niederhauser, T. L., et al., Journal of Chromatography A, 804:69-77 (1998); Lamb, J. D., et al., Talanta, 39(8):923-930 (1992); and Smith, R. G., et al., Journal of Chromatography A, 671:89-94 (1994).
The majority of adsorbed materials have limited number of applications due to their incompatibility with the solvents that elute the adsorbed functional layer. There is also a restriction on using these materials at elevated temperatures. Covalent attachment reduces these problems. Previously reported substrates with covalently attached macrocycles include silica gel, polymeric resins, thin films and others (Blasius, E., et al., Pure & App. Chem. 54(11):2115-2128 (1982); Montanari, F., et al., British Polymer Journal, 16:212-218 (1984); U.S. Pat. No. 5,393,892 to Krakowiak, et al.; U.S. Pat. No. 4,943,375 to Bradshaw, et al.; U.S. Pat. No. 5,968,363 to Riviello, et al.; JP Patent No. 55018434A2 to Kakiuchi, et al.; JP Patent No. 59145022A2 to Fujine, et al.; JP Patent No. 61033220A2 to Fujine, et al.; JP Patent No. 4346064A2 to Watanabe, et al.; and PCT Publication W099/28355 to Darling, et al.
Many strategies for the synthesis of macrocyclic compounds have been developed over the years (Comprehensive Supramolecular Chemistry Vol. 1-10, Jean-Marie Lehn—Chairman of the Editorial Board, 1996 Elsevier Science Ltd.; Krakowiak, K. E., et al., Israel Journal of Chemistry 32:3-13 (1992); Bradshaw, J S., et al., “Aza-Crown Macrocycles,” The Chemistry of Heterocyclic Compounds, Vol. 51, ed. Taylor, E. C., Wiley, New York, 1993; Haoyun, A., et al., Chemical Reviews 92:543-572 (1992)). However, the synthesis of functionalized macrocycles is difficult. Hydroxy, amino and carboxylic groups added to linear precursors before the ring closure step are commonly used functionalities for derivatization of macrocycles. Most of the synthetic procedures imply protection of these groups prior to cyclization. Protected groups are chemically transformed into desired functions after the macroring is constructed (Krespan, C. G., Journal of Organic Chemistry 45:1177-1180 (1980); Montanari, F., et al., Journal of Organic Chemistry 47:1298-1302 (1982); Haoyun, A., et al., Journal of Organic Chemistry 57:4998-5005 (1992)). This methodology can impose considerable limitations on synthesis and purification of functionalized macrocycles, especially bicyclic and polycyclic compounds. Synthetic difficulties can lead to low overall yields and high production costs of these materials.
Macrocyclic compounds containing allylic functionalities are known from prior art (Krakowiak, K. E., et al., Journal of Heterocyclic Chemistry 27:1011-1014 (1990)). Some of them were further hydrosilated and attached to silica solid supports (Bradshaw, J. S., et al., Pure & Appl. Chem. 61:1619-1624 (1989); Bradshaw, J. S., et al., Journal of Inclusion Phenomena and Molecular Recognition in Chemistry 7:127-136 (1989)). The synthesis of allyl containing [2.2.2] cryptand 1 has been reported (Babb, D. A., et al., Journal of Heterocyclic Chemistry 23:609-613 (1986)).
The methods for covalent attachment of the cryptands to polymeric substrates are based mostly on the interaction of active layer of a substrate, for example, benzyl chloride groups with hydroxyl or amino functionalized cryptand molecules (Montanari, F., et al., J. Org. Chem., 47:1298-1302 (1982); Montanari, F., et al., British Polymer Journal, 16:212-218 (1984) and Montanari, F., et al., Tetrahedron Letters, No 52, 5055-5058 (1979)). This interaction also involves the side process—formation of the quaternary centers from the tertiary nitrogens of the macrocycle (Montanari, F., et al., British Polymer Journal, 16:212-218 (1984). Quaternisation causes extended decomposition of the macrocycle via Hofmann degradation reducing the capacity of the anion exchange stationary phase. An amide group is another linker reported for a covalent functionalization of the substrates with cryptand molecules (Montanari, F., et al., British Polymer Journal, 16:212-218 (1984). Amides do not withstand the extremely high pHs used in anion exchange chromatography. Moreover, most of the described synthetic for producing hydroxyl or amino functionalized cryptands, are not practical to satisfy the requirements of industrial scale production.
There is a need to provide an improved method for covalent bonding of cryptands to a substrate for uses such as a chromatographic separation medium to separate anions.